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Biomedical subjects

M C Dolan

Publications and source records attributed to M C Dolan.

36 records · Page 2Linked to original sources
PubMed1998

Vector competence of Ixodes scapularis and Ixodes ricinus (Acari: Ixodidae) for three genospecies of Borrelia burgdorferi.

The vector competence of 2 tick species, Ixodes ricinus (L.) and Ixodes scapularis Say, was determined and compared for 3 genospecies of Borrelia burgdorferi. The 3 genospecies of B. burgdorferi used in the following experiments were Borrelia burgdorferi sensu stricto (B-31 and B-31.D1 clone), Borrelia afzelii (strain Pgau. C3), and Borrelia garinii (strain VS286 and VSBP). Spirochetes from all 5 strains were inoculated intradermally into outbred mice; larval ticks of both species were subsequently fed on those mice and replete larvae were assayed for infection by culture in BSK-H media every 7 d for 4 wk. Infection frequencies in I. scapularis exposed to the 5 strains were as follows: B-31 (90%), B-31.D1 (83%), Pgau.C3 (87%), VS286 (10%), and VSBP (5%). The comparable infection frequencies for I. ricinus were B-31 (3%), B-31.D1 (3%), Pgau.C3 (90%), VS286 (5%), and VSBP (3%). Resultant nymphal I. scapularis successfully transmitted B-31, B-31,D1, Pgau.C3, and VS286 to outbred mice. I. ricinus nymphs transmitted Pgau.C3 and VS286. Both species failed to transmit strain VSBP.

Animals↗
PubMed1997

Vector competence of Ixodes scapularis, I. spinipalpis, and Dermacentor andersoni (Acari:Ixodidae) in transmitting Borrelia burgdorferi, the etiologic agent of Lyme disease.

This report describes the vector competence of 3 ixodid tick species, Ixodes scapularis (Say), I. spinipalpis (Nuttall), and Dermacentor andersoni (Stiles), for Borrelia burgdorferi in Colorado. The study was based on preliminary field work performed in 6 Colorado counties, where rodents and ticks were collected and assayed for the presence of B. burgdorferi. Four of the 6 counties produced 52 rodent and 39 I. spinipalpis isolates of B. burgdorferi. Two B. burgdorferi isolates were tested under laboratory conditions and found to be infective to Imperial Cancer Research Fund (ICRF) outbred mice. The 1st, a low-passage strain originating from New York (B-31, passage 6) was used as a control, and the 2nd was isolated from ear tissue of a Neotoma mexicana (Baird) (Mexican wood rat) that was trapped in Colorado. Larvae of I. scapularis, I. spinipalpis. and D. andersoni were fed on infected mice and cultured in Barbour-Stoner-Kelly media to assay for infection at 1, 2, 3, and 4 wk after repletion. The infection rates in replete larvae. were 75, 69, and 8.5%, respectively, whereas transstadial nymphal infection rates were 80, 75, and 0%, respectively. Both I. scapularis and I. spinipalpis were shown to be competent vectors that acquired the infection from the host reservoir mice and subsequently transmitted it to naive mice. Given that I. scapularis are not found in Colorado, I. spinipalpis are restricted to the nests and burrows of rodents, and because of the semiarid environment in Colorado, the risk of human contact with B. burgdorferi appears to be low.

Animals↗
PubMed1997

Duration of immunity to reinfection with tick-transmitted Borrelia burgdorferi in naturally infected mice.

The ability of naturally infected and cured mice to resist reinfection with tick-transmitted Borrelia burgdorferi was tested over a 1-year period. All of the mice were resistant to reinfection when they were challenged at 1.5 months after cure. The majority of animals were resistant to reinfection for up to 10.5 months after cure, but this resistance was lost at 1 year after cure. Both protected and unprotected animals showed a diverse array of antibodies on Western immunoblots. Protection was not associated with the killing of spirochetes in ticks, and naturally infected mice produced no antibodies to outer surface protein A (OSP A). The titers to whole Borrelia sonicate and OSP C, however, remained high throughout the 1-year study period. The levels of borreliacidal antibodies were highest in the 1.5 month-after-cure group. Natural immunity to reinfection with B. burgdorferi is limited in time, is complex, and may involve both humoral and cellular components.

Animals↗
PubMed1997

Reactivity with a specific epitope of outer surface protein A predicts protection from infection with the Lyme disease spirochete, Borrelia burgdorferi.

The response to recombinant vaccines for Lyme disease was studied to determine serum antibody levels effective in protecting against tick-transmitted infection. Data presented here demonstrate a significant correlation between antibody to an epitope on outer surface protein A (OspA) and protection against infection with Borrelia burgdorferi in canines and mice. A competitive enzyme-linked immunosorbent assay was developed to measure antibody to a site on OspA, defined by monoclonal antibody LA-2. Comparison of LA-2 titers against infection of canines and mice following vaccination and challenge established a predicted value for LA-2 titers. The statistical relationship between serum antibody levels and protection was calculated by logistic regression analysis. The statistical model predicted that an LA-2 titer of 0.32 microg equivalents (eq) per ml correlated to an 80% predicted probability of protection for both mice and dogs. This value was used to classify mice and dogs as to their protected status at the time of tick exposure. The LA-2 cutoff titer (0.32 microg eq/ml) correctly classified all dogs (n = 13) and mice (n = 44) that failed to become infected. By contrast, 20 of 22 dogs and 28 of 31 mice with titers of less than 0.32 microg eq/ml became infected. On the basis of these results, we conclude that an LA-2 titer is a reliable indicator of immune status for estimating immune protection following use of OspA-based vaccines for B. burgdorferi sensu stricto.

Animals↗
PubMed1996

Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC.

Outbred mice were immunized with the soluble fraction of a crude Escherichia coli lysate containing either recombinant outer surface protein C (OspC or P39 of Borrelia burgdorferi B31 (low passage). Following seroconversion, the mice were challenged with an infectious dose of B. burgdorferi B31 via the natural transmission mode of tick bite. Three mice immunized with P39 were not protected; however, all 12 of the recombinant OspC-immunized mice were protected from infection as assayed by culture and serology. Although OspC has been shown to be a protective immunogen against challenge with in vitro-cultured borrelia administered by needle, this study is the first to demonstrate OspC effectiveness against tick-borne spirochetes. Following feeding, all ticks still harbored B. burgdorferi, suggesting that the mechanism of protection is not linked to destruction of the infectious spirochete within the tick. In a separate experiment, groups of four mice were immunized with protein fractions from B. burgdorferi B31 purified by preparative gel electrophoresis in an attempt to identify potential protective antigens. Many of these mice developed high-titer-antibody responses against OspC, but curiously the mice were susceptible to B. burgdorferi infection via tick bite. These results suggest that the protective epitope(s) on OspC is heat sensitive/conformational, a finding which has implications in vaccine development.

Animals↗
PubMed1996

Ability of experimentally infected chickens to infect ticks with the Lyme disease spirochete, Borrelia burgdorferi.

Chickens were used as a laboratory model to determine the conditions affecting the ability of birds to infect ticks with Lyme disease spirochetes. Chicks (Gallus gallus) were exposed to 12 nymphal Ixodes scapularis at one week or three weeks of age. Xenodiagnostic larval ticks fed these birds at weekly intervals thereafter. Chicks exposed to infected nymphs at one week of age infected 87% of larvae at three weeks of age, but only infected 3% of larvae at four weeks and 0% of larvae at five weeks. Chicks exposed to nymphs at three weeks of age infected only 12% of larvae at four weeks, and 0% thereafter. Thus, experimentally infected chicks can infect larval ticks, but only for a brief interval after exposure. Young chicks are more infectious than older chickens. The immune response of infected chicks was rapid and directed against diverse antigens.

Animals↗
PubMed1995

Induction of an outer surface protein on Borrelia burgdorferi during tick feeding.

Lyme disease spirochetes, Borrelia burgdorferi sensu lato, are maintained in zoonotic cycles involving ticks and small mammals. In unfed ticks, the spirochetes produce one outer surface protein, OspA, but not OspC. During infection in mammals, immunological data suggest that the spirochetes have changed their surface, now expressing OspC but little or no OspA. We find by in vitro growth experiments that this change is regulated in part by temperature; OspC is produced by spirochetes at 32-37 degrees C but not at 24 degrees C. Furthermore, spirochetes in the midgut of ticks that have fully engorged on mice now have OspC on their surface. Thus two environmental cues, an increase in temperature and tick feeding, trigger a major alteration of the spirochetal outer membrane. This rapid synthesis of OspC by spirochetes during tick feeding may play an essential role in the capacity of these bacteria to successfully infect mammalian hosts, including humans, when transmitted by ticks.

Animals↗
PubMed1995

The Lyme disease vaccine candidate outer surface protein A (OspA) in a formulation compatible with human use protects mice against natural tick transmission of B. burgdorferi.

Development of a vaccine for the Lyme disease spirochete, Borrelia burgdorferi, has focused on the bacterial lipoprotein, major outer surface protein A (OspA). With few exceptions, testing of OspA vaccines in animal models has involved challenge with needle inoculation of cultured spirochetes. Recombinant OspA proteins from two OspA divergent strains of B. burgdorferi were tested for their vaccine potential in three different strains of mice challenged with laboratory reared ticks with a high rate of B. burgdorferi infection. All formulations of the B. burgdorferi sensu stricto derived OspA vaccine protected all strains of mice when challenged by ticks infected with an OspA homologous strain of the spirochete, whereas heterologous OspA from B. afzelii did not protect. Furthermore, ticks feeding on protected mice had reduced OspA levels compared to unvaccinated controls.

Animals↗
PubMed1995

Variation in antigenicity and infectivity of derivatives of Borrelia burgdorferi, strain B31, maintained in the natural, zoonotic cycle compared with maintenance in culture.

The original isolate of Borrelia burgdorferi, strain B31, can be maintained in vitro indefinitely. A number of studies have demonstrated that there are recognizable changes in the genetic composition of the spirochete after more than 60 passages. We have maintained B31 in the natural zoonotic cycle of transmission of infection between laboratory mice and laboratory-reared Ixodes ticks. To determine whether similar changes occur in the natural transmission cycle, we reisolated strain B31 from mouse skin at the fifth zoonotic cycle. This reisolated derivative had the same infectivity as the parent B31 strain, had lost the 8-kb supercoiled plasmid present in B31, and induced a gross serum antibody response indistinguishable from the B31 immune response. Analysis of antigen expression with monoclonal antibodies generated against B31, however, showed differential expression of a subset of antigens between B31 and the isolated derivative.

Animals↗
PubMed1994

The Criminal Procedure (Insanity and Unfitness to Plead) Act, 1991. A case report and selected review of the legal reforms.

Procedures relating to Insanity and Fitness to Plead are reviewed with special emphasis on the problems encountered with previous legislation. The introduction of the new Criminal Procedure (Insanity and Unfitness to Plead) Act 1991, on 1 January 1992, offered greater discretion in the disposal of these defendants, but fell short of many of the recommendations made by those advocating reform. As yet, too few cases have passed through the courts to highlight particular deficiencies in the unreformed parts of the Act, but the benefits are already apparent. Finally, some of the potential pitfalls of supervision and treatment orders and other disposals are discussed and an insanity case, dealt with under the new legislation, is presented.

Adult↗
PubMed1989

Evaluation of the validity of the Done nomogram in the management of acute salicylate intoxication.

To evaluate the validity of the Done nomogram in the management of acute adult salicylate intoxications, a retrospective review of cases at our institution was performed. The degree of severity (ie, asymptomatic, mild, moderate, or severe) as determined by plotting the serum concentration and time on the nomogram for 55 acute salicylate intoxications was compared with the degree of severity decided on by three experienced emergency physicians who based their decision on the clinical presentation of the cases and the original criteria devised by Done for each category of severity. Discordant classifications between the nomogram and the physicians provided a basis on which a predictive index for the nomogram and various subsets of cases could be determined. The calculated predictive index for the nomogram was 0.42, with the highest predictive index of 0.79 in the mild salicylate category. The nomogram tends to overpredict the severity of intoxication in the moderate and severe categories. There was no significant difference between predictive indexes of mixed versus nonmixed or enteric-coated acetylsalicylic acid versus plain acetylsalicylic acid cases, although the nomogram had a higher predictive index when used for concentrations drawn six to 12 hours after ingestion (P less than .01, Fisher's exact test). Decisions on management of an acute salicylate overdose should be based on clinical presentation and good judgment as well as the serum salicylate concentration in relation to the time of ingestion.

Adult↗
PubMed1989

Prehospital blind nasotracheal intubation by paramedics.

Blind nasotracheal intubation attempts by paramedics in the field were prospectively reviewed. In particular, we analyzed the frequency, success rate, complication rate, frequency of performance by each paramedic, indications, and patient outcome. Blind nasotracheal intubation was attempted in 324 patients and successful in 231. The average success rate for medical patients was 72.2% (195 of 270 attempts) and for trauma patients was 66.7% (36 of 54 attempts). This difference was not significant (P greater than .05). Even with 59.8% of the 82 participating paramedics attempting blind nasotracheal intubation less than four times over the 19-month study period, the average success rate was 71.3%. There was a significant increase in success when blind nasotracheal intubation was attempted more than three times during the study period (P less than .005). Major complications occurred in 0.9% (three) of the patients. The overall complication rate was 13% (42). The incidence of complications tended to decline with increasing paramedic frequency but did not reach statistical significance (P greater than .05). Blind nasotracheal intubation is a safe initial field airway approach in spontaneously breathing patients in whom there are no contraindications. Even with a low frequency of performance, success and complication rates are acceptable.

Allied Health Personnel↗
PubMed1987

Carboxyhemoglobin levels in patients with flu-like symptoms.

Subacute carbon monoxide poisoning is commonly misdiagnosed as an influenza-like viral illness. All patients presenting to the triage nurse at University Hospital with flu-like symptoms during February 1985 were asked to give blood samples for carboxyhemoglobin determination. Fifty-five patients (10% of those eligible) with headache, dizziness, nausea, vomiting, diarrhea, weakness, general malaise, or shortness of breath were enrolled in the study. Carboxyhemoglobin levels ranged from 0 to 21%. Thirteen patients (23.6%) of this self-selected subgroup had carboxyhemoglobin levels greater than or equal to 10%. There was no statistically significant difference in carboxyhemoglobin levels between smokers and nonsmokers. More patients using wood heat had elevated carboxyhemoglobin levels than patients using any other form of heating (P less than .05). No patient with a carboxyhemoglobin level greater than or equal to 10% was diagnosed as having subacute CO poisoning by emergency physicians. Physicians must seek out the possibility of CO toxicity in patients with flu-like illness, particularly in inner-city populations during the heating months. Fundoscopy and COHb levels may be useful in selected cases to correctly diagnose patients and avoid a return to a hazardous environment with potentially fatal consequences.

Adolescent↗
PubMed1987

Canine von Willebrand factor expresses a multimeric composition similar to human von Willebrand factor.

Canine von Willebrand factor (vWf) was compared to human vWf. Antisera raised against human vWf or canine vWf cross-reacted with both heterologous proteins and reactions of partial identity were seen using crossed immunoelectrophoresis. Similar patterns of multimerization were obtained for vWf from both canine and human sources using the enzyme-linked immunoelectrotransfer blot method. However, the canine protein displayed an altered electrophoretic mobility. The molecular weight of the vWf monomer was estimated by SDS-PAGE and found to be indistinguishable from that of human vWf monomer. Canine vWf is decreased in animals with clinically evident hypothyroidism and in heterozygous "carriers" of von Willebrand's disease (vWd) that display no clinical symptoms of vWd. Results expand the concept that von Willebrand's disease in dogs may be a useful model for study of vWd in humans, and that immunochemical methods established for studies of human vWf appear appropriate for studies of canine vWf.

Animals↗
PubMed1985

Carbon monoxide poisoning.

Carbon monoxide poisoning is a significant cause of illness and death. Its protean symptoms probably lead to a gross underestimation of its true incidence. Low levels of carbon monoxide aggravate chronic cardiopulmonary problems, and high levels are associated with cardiac arrhythmias and cerebral edema. Patients who survive acute poisoning are at risk of delayed neurologic sequelae. The measurement of carboxyhemoglobin levels does not reveal the tissue levels of carbon monoxide but is useful in determining therapy. Treatment includes the monitoring and management of cardiac arrhythmias and oxygenation. Hyperbaric oxygenation is beneficial, but there are currently no definite criteria for its use.

Carbon Monoxide Poisoning↗